1. Field of the Invention
The invention relates to a process for producing a hydrophobic membrane using a thermally induced phase separation process, the membrane having a sponge-like, open-pored, microporous structure. The invention relates further to an integrally asymmetrical, hydrophobic membrane for gas exchange that is composed primarily of at least one polymer selected from the group of polyolefins and has a first and a second surface, the membrane having a support layer with an open-pored, microporous structure and adjacent to this support layer at least at one of the surfaces a separation layer with denser structure, and to the use of such membrane for blood oxygenation.
2. Description of Related Art
In a multitude of applications in the fields of chemistry, biochemistry, or medicine, the problem arises of separating gaseous components from liquids or adding such components to the liquids. For such gas exchange processes, there is increasing use of membranes that serve as a separation membrane between the respective liquid, from which a gaseous component is to be separated or to which a gaseous component is to be added, and a fluid that absorbs or releases this gaseous component. The fluid in this case can be either a gas or a liquid containing the gas component to be exchanged or capable of absorbing it. Using such membranes, an exchange surface can be provided for gas exchange and, if required, direct contact between the liquid and fluid can be avoided.
An important application of membrane-based gas exchange processes in the medical field is for oxygenators, also called artificial lungs. In these oxygenators, which are used in open-heart operations, for example, oxygenation of blood and removal of carbon dioxide from the blood take place. Generally, bundles of hollow-fiber membranes are used for such oxygenators. Venous blood flows in the exterior space around the hollow-fiber membranes, while air, oxygen-enriched air, or even pure oxygen is passed through the lumen of the hollow-fiber membranes. Via the membranes, there is contact between the blood and the gas, enabling transport of oxygen into the blood and simultaneously transport of carbon dioxide from the blood into the gas.
In order to provide the blood with sufficient oxygen and at the same time to remove carbon dioxide from the blood to a sufficient extent, the membranes must ensure a high degree of gas transport: a sufficient amount of oxygen must be transferred from the gas side of the membrane to the blood side and, conversely, a sufficient amount of carbon dioxide from the blood side of the membrane to the gas side, i.e., the transfer rates, expressed as the gas volume transported per unit of time and membrane surface area from one membrane side to the other, must be high. A decisive influence on the transfer rates is exerted by the porosity of the membrane, since only in the case of sufficiently high porosity can adequate transfer rates be attained.
A number of oxygenators are in use that contain hollow-fiber membranes with open-pored, microporous structure. One way to produce this type of membrane for gas exchange, such as for oxygenation, is described in DE-A-28 33 493. Using the process in accordance with this specification, membranes can be produced from meltable thermoplastic polymers with up to 90% by volume of interconnected pores. The process is based on a thermally induced phase separation process with liquid-liquid phase separation. In this process, a homogeneous single-phase melt mixture is first formed from the thermoplastic polymer and a compatible component that forms a binary system with the polymer, the system in the liquid state of aggregation having a range of full miscibility and a range with a miscibility gap, and this melt mixture is then extruded into a bath that is essentially inert with respect to the polymer and has a temperature lower than the demixing temperature. In this way, a liquid-liquid phase separation is initiated and the thermoplastic polymer solidified to form the membrane structure.
An improved process for producing such membranes, which permits specific adjustment of the pore volume, size, and wall, is disclosed in DE-A-32 05 289. In this process, 5-90% by weight of a polymer is dissolved, by heating to above the critical demixing temperature Tc, in 10-95% by weight of a mixture of two compounds that are liquid and miscible at the solution temperature, whereby the employed mixture of polymer and compounds A and B has a miscibility gap in the liquid state of aggregation, compound A is a solvent for the polymer, and compound B increases the phase separation temperature of a solution consisting of the polymer and compound A. The solution is then given shape and by cooling brought to demixing and solidifying, and the compounds A and B are subsequently extracted.
The membranes disclosed in accordance with DE-A-28 33 493 or DE-A-32 05 289 have an open-pored, microporous structure and also open-pored, microporous surfaces. On the one hand, this has the result that gaseous substances, such as oxygen or carbon dioxide, can pass through the membrane relatively unrestricted and the transport of a gas then takes place as a Knudsen flow or Knudsen diffusion, combined with relatively high transfer rates for gases. On the other hand, however, in extended use of these membranes in blood oxygenation or generally in gas exchange processes with aqueous liquids, blood plasma or a portion of the liquid can penetrate into the membrane and, in the extreme case, exit on the gas side of the membrane, even if in these cases the membranes are produced from hydrophobic polymers, in particular polyolefins. This results in a drastic decrease in gas transfer rates. For medical applications for blood oxygenation, this is termed plasma breakthrough.
The plasma breakthrough time of such membranes, as producible in accordance with DE-A-28 33 493 or DE-A-32 05 289, is sufficient in most cases of conventional blood oxygenation to oxygenate a patient in a normal open-heart operation. However, the desire exists for membranes with higher plasma breakthrough times in order to attain higher levels of safety in extended heart operations and to rule out the possibility of a plasma breakthrough that would require immediate replacement of the oxygenator. A frequently demanded minimum value in this connection for the plasma breakthrough time is 20 hours. The aim, however, is also to be able to oxygenate premature infants or in general patients with temporarily restricted lung function long enough until the lung function is restored, i.e., to be able to conduct long-term oxygenation. Prerequisites for this are appropriately long plasma breakthrough times.
From EP-A-299 381, hollow-fiber membranes for oxygenation are known that have plasma breakthrough times of more than 20 hours, i.e., there is no plasma breakthrough even under extended use. With the otherwise porous membrane with cellular structure, this is attained by a barrier layer that has an average thickness, calculated from the oxygen and nitrogen flow, not exceeding 2 xcexcm and is substantially impervious to ethanol. The membrane is essentially free of open pores, i.e., pores that are open both to the outside and to the inside of the hollow-fiber membrane. The membranes in accordance with EP-A-299 381 have a porosity of at most 50% by volume, since at higher porosity values the pores are interconnected and communication occurs between the sides of the hollow-fiber membranes, resulting in plasma breakthrough. In the barrier layer, the transport of gases to be exchanged is effected by solution diffusion.
The production of these membranes is conducted via a melt-drawing process, i.e., the polymer is first melt-extruded to a form a hollow fiber and then hot- and cold-drawn. In this case, only relatively low porosity values are obtained, which means that, in conjunction with the transport occurring in the barrier layer via solution diffusion, the attainable transfer rates for oxygen and carbon dioxide remain relatively low. Moreover, while the hollow-fiber membranes in accordance with EP-A-299 381 exhibit sufficient tensile strength as a result of the pronounced drawing in conjunction with manufacture, they have only a small elongation at break. In subsequent textile processing steps, such as to produce bundles of hollow-fiber mats, which have proven excellent in the production of oxygenators with good exchange performance and as are described in EP-A-285 812, for example, these hollow-fiber membranes are therefore not conducive to processing.
Typically, in melt-drawing processes, membranes are formed with slit-shaped pores with pronounced anisotropy, the first main extension of which is perpendicular to the drawing direction and the second main extension perpendicular to the membrane surface, i.e., in the case of hollow-fiber membranes runs between the exterior and interior surfaces of the membrane, whereby the channels formed by the pores run in a relatively straight line between the surfaces. In the case in which, for example, mechanical damage in the spinning process causes leaks in the barrier layer, a preferred direction then exists for the flow of a liquid between the interior and exterior surfaces or vice-versa, thereby promoting plasma breakthrough.
It is therefore an object of the invention to provide a process with a wide variety of applications and with which membranes can be produced for gas exchange that exhibit only to a reduced extent, if at all, the disadvantages of the prior art membranes, permit high gas exchange performance, are impervious at least over extended periods of time to the breakthrough of hydrophilic liquids, in particular blood plasma, and have good qualities for further processing.
It is a further object of the invention to provide membranes for gas exchange in which the disadvantages of the prior art membranes are at least reduced, that have a high capacity for gas exchange, are resistant at least over extended periods of time to the breakthrough of hydrophilic liquids, in particular blood plasma, and exhibit good qualities for further processing.